Photosensitization of cells with different metastatic potentials by liposome-delivered Zn(II)-phthalocyanine.
The phototoxicity of liposome-incorporated Zn(II)-phthalocyanine (ZnPc) and its water-soluble tetrasulphonated derivative (ZnPcTS) was studied in the tumorigenic but nonmetastatic (RE4) and the highly metastatic (4R) transformed rat embryo fibroblasts. Upon irradiation with 585-605 nm light in the presence of ZnPc, the cell survival drastically decreased, while it was unaffected by ZnPcTS. Enzymatic assays showed that ZnPc induced about a 60% decrease in the activity of the mitochondrial enzymes NADH and succinate dehydrogenase after 3 min of irradiation, while no significant reduction in the activity of lactate dehydrogenase and lysosomal N-acetyl-beta-glucosaminidase was observed. The transport of thymidine, deoxyglucose and alpha-aminoisobutyric acid through the plasma membrane was strongly inhibited after irradiation. Similarly, the intracellular ATP content was significantly reduced. The reduction of DNA biosynthesis showed a time dependence quite similar to the photo-induced decrease in cell survival. No repair of cellular functions affected by ZnPc was observed in the 2 cell lines. These results indicate that, under our experimental conditions, hydrophobic ZnPc exerts its cytotoxic activity mainly by impairing those functions localized in the plasma membrane of the cells.
Valduga
G
G
Department of Biology, University of Padua (Padova), Italy. valduga@civ.bio.unipd.it
Reddi
E
E
Garbisa
S
S
Jori
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004337:Drug Carriers; D007211:Indoles / Q000008:administration & dosage*; D054833:Isoindoles; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000008:administration & dosage*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D051381:Rats; D017967:Zinc Compounds
D004273:DNA, Neoplasm; D004337:Drug Carriers; D007211:Indoles; D054833:Isoindoles; D008081:Liposomes; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011838:Radiation-Sensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; C052735:zinc tetrasulfophthalocyanine; D000255:Adenosine Triphosphate